A Proteomic Analysis of the Plasma Glycoproteins of a MCF-7 Mouse Xenograft: A Model System for the Detection of Tumor Markers

Orazine, Christina; Hincapie, Marina; Hancock, William S.; Hattersley, Maureen M.; Hanke, Jeff H.

doi:10.1021/pr7008516

Cited by 23 publications

(27 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IRAK4 was first observed in the serum of both normal individuals and those with renal carcinoma (39). Further, host peptides corresponding to the IRAK4 XCT (aa 417-441) were isolated from the serum of MCF7 BrCa xenografted mice (40). These findings prompt intriguing questions about the biological impact of IRAK4 trafficking and processing and the role of the XCT fragment.…”

Section: Discussionmentioning

confidence: 99%

IRAK4 and TLR3 Sequence Variants may Alter Breast Cancer Risk among African-American Women

et al. 2013

View full text Add to dashboard Cite

Mounting evidence suggests that imbalances in immune regulation contribute to cell transformation. Women of African descent are an understudied group at high risk for developing aggressive breast cancer (BrCa). Therefore, we examined the role of 16 innate immune single nucleotide polymorphisms (SNPs) in relation to BrCa susceptibility among 174 African-American women in Atlanta, GA, USA. SNPs were examined in germ-line DNA collected from 102 BrCa patients and 72 women with benign nodules using SNPstream methodology. Inheritance of the TLR3 rs10025405 GG genotype was associated with an 82% decrease in BrCa risk. In contrast, individuals who possessed at least one IRAK4 rs4251545 T allele had a 1.68- to 4.99-fold increase in the risk of developing BrCa relative to those with the referent genotype (OR = 4.99; 95% CI = 1.00, 25.00; p = 0.0605). However, the IRAK4 rs4251545 locus was only significant under the additive genetic model (p trend = 0.0406). In silico predictions suggest IRAK4 rs4251545 SNP falls within a transcription enhancer/silencer region of the gene and codes for an Ala428Thr amino acid change. This missense mutation introduces a potential phosphorylation site in the extreme carboxy terminus (XCT) of the IRAK4 kinase domain. Preliminary molecular modeling predicts that this SNP stabilizes two alpha helices within the XCT on the surface of the IRAK4 kinase domain and increases the size of the groove between them. Our in silico results, combined with previous reports noting the presence of IRAK4 and XCT fragments in mouse and human serum, suggest the possibility that the XCT subdomain of IRAK4 possesses biological function. These findings require further evaluation and validation in larger populations, additional molecular modeling as well as functional studies to explore the role of IRAK4 and its XCT in cell transformation and innate immunity.

show abstract

Section: Discussionmentioning

confidence: 99%

IRAK4 and TLR3 Sequence Variants may Alter Breast Cancer Risk among African-American Women

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Recently, other groups undertook various strategies to detect biomarkers for different diseases in plasma and serum. These strategies include isobaric labeling (Bennett et al 2011), biomarker enrichment by application of low-frequency ultrasound to tumor cells (D'Souza et al 2009) and concentration of subsets of plasma proteins, glycoproteins (Orazine et al 2008) and phosphoproteins (Ye et al 2010)), which are enriched prior to biomarker detection by mass spectroscopy. In contrast to these approaches, our strategy is broad based, to get access to the majority of potential biomarkers; however, DIGE gel image analysis with DeCyder 6.5 resulted in a list of differentially expressed protein spots between both diagnostic groups (Karp et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Multidimensional plasma protein separation technique for identification of potential Alzheimer’s disease plasma biomarkers: a pilot study

et al. 2012

View full text Add to dashboard Cite

Neurochemical differential diagnosis between Alzheimer's disease and other dementias is currently based on CSF biomarkers. Here, we report a method by which potential biomarkers can be identified in blood. Blood plasma samples from seven well-characterized Alzheimer's patients and seven non-Alzheimer's patients were subjected to a multi-dimensional protein separation procedure. After removal of 12 high-abundance proteins, the depleted samples from both diagnostic groups were labeled with different fluorescent dyes, mixed and separated by anion exchange and RP-chromatography. The resulting chromatography fractions were analyzed on 2D-gels. Twenty significant differentially expressed proteins were identified by mass spectrometry analysis. Ten of these proteins were either involved in the pathophysiology of Alzheimer's disease or the amyloid/Aβ-peptide processing pathway. This work demonstrated a successful application of a multidimensional separation technique and holds the potential to identifying blood-based biomarkers for other diseases in the future.

show abstract

“…These biomarkers could be potentially useful for prognosticating (helping to determine outcome), but they are conceivably valuable in surveillance (assessing recurrent disease). This notion is being addressed by numerous proteomic researchers, and though mounting evidence suggests that a variety of serum/plasma biomarkers may be clinically useful in breast cancer, 2,3 there are currently no serum/plasma biomarker assays available for systematic clinical use to monitor breast cancer progression.…”

Section: Introductionmentioning

confidence: 99%

Reevaluating Cathepsin D as a biomarker for breast cancer: Serum activity levels versus histopathology

Abbott¹,

Margaryan²,

Jeruss³

et al. 2010

Cancer Biology & Therapy

View full text Add to dashboard Cite

Cathepsin D is a lysosomal hydrolase involved in intra- and extracellular proteolysis. This enzyme is aberrantly produced and processed in malignancy, and most notably is over-secreted into the tumor cell microenvironment. This hyper-secretion may lead to excessive degradation of the extracellular matrix, and contribute to tumor progression and metastases. These phenomena have been established in vitro, and there is evidence that Cathepsin D is similarly dysregulated in human breast cancer patients. Because breast cancer lacks an effective screening or surveillance biomarker, here we address the hypothesis that serum Cathepsin D activity may be useful to assess the presence or progression of breast cancer in females. While representative histologic sections from various disease-specific cohorts confirm previous findings that increased Cathepsin D production and secretion correlate with tumor progression, we report no difference in serum Cathepsin D activity between patients who are disease-free, patients with pre-invasive or limited invasive disease, and patients with metastatic disease. Furthermore, in patients with known metastatic disease, there were no clinical variables associated with significantly different serum Cathepsin D activity. however, the immunohistochemical localization of Cathepsin D expression in histopathologic sections from breast cancer patients correlates with disease progression. Based on the serum results, and in contradistinction to Cathepsin D localization in breast cancer tissues, our findings support using Cathepsin D as a reliable histopathology biomarker for disease progression, but not for serum screening.

show abstract

A Proteomic Analysis of the Plasma Glycoproteins of a MCF-7 Mouse Xenograft: A Model System for the Detection of Tumor Markers

Cited by 23 publications

References 80 publications

IRAK4 and TLR3 Sequence Variants may Alter Breast Cancer Risk among African-American Women

IRAK4 and TLR3 Sequence Variants may Alter Breast Cancer Risk among African-American Women

Multidimensional plasma protein separation technique for identification of potential Alzheimer’s disease plasma biomarkers: a pilot study

Reevaluating Cathepsin D as a biomarker for breast cancer: Serum activity levels versus histopathology

Contact Info

Product

Resources

About